Polythiazide

Identification

Summary

Polythiazide is a thiazide diuretic used in the management of hypertension and treatment of edema.

Brand Names
Minizide, Renese, Renese-R
Generic Name
Polythiazide
DrugBank Accession Number
DB01324
Background

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 439.882
Monoisotopic: 438.970880311
Chemical Formula
C11H13ClF3N3O4S3
Synonyms
  • Polythiazide

Pharmacology

Indication

Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofEdema••••••••••••••••••
Management ofEdema••••••••••••••••••
Management ofEdema••••••••••••••••••
Management ofEdema••••••••••••••••••
Management ofEdema••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure

Mechanism of action

As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.

TargetActionsOrganism
ASolute carrier family 12 member 3
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
Polythiazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirPolythiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbaloparatideAbaloparatide may increase the hypotensive activities of Polythiazide.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Polythiazide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Polythiazide.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Polythiazide.
Food Interactions
  • Avoid alcohol. Alcohol may potentiate orthostatic hypotension.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ReneseTablet1 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
ReneseTablet4 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
ReneseTablet2 mg/1OralPfizer Labs2005-12-14Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (5 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (2 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
MinizidePolythiazide (0.5 mg/1) + Prazosin hydrochloride (1 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUS flag
Renese-RPolythiazide (2 mg/1) + Reserpine (25 mg/1)TabletOralUNSPECIFIED2006-02-06Not applicableUS flag

Categories

ATC Codes
C03AA05 — PolythiazideG01AE10 — Combinations of sulfonamidesC03AB05 — Polythiazide and potassium
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiadiazines
Sub Class
Benzothiadiazines
Direct Parent
1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Organopnictogen compounds / Organofluorides
show 4 more
Substituents
1,2,4-benzothiadiazine-1,1-dioxide / Alkyl fluoride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiadiazine (CHEBI:8327)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
36780APV5N
CAS number
346-18-9
InChI Key
CYLWJCABXYDINA-UHFFFAOYSA-N
InChI
InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)
IUPAC Name
6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O

References

General References
Not Available
Human Metabolome Database
HMDB0015419
KEGG Drug
D00657
KEGG Compound
C07766
PubChem Compound
4870
PubChem Substance
46508633
ChemSpider
4704
RxNav
8565
ChEBI
8327
ChEMBL
CHEMBL1587
Therapeutic Targets Database
DAP000751
PharmGKB
PA164748763
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Polythiazide

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
Dosage Forms
FormRouteStrength
CapsuleOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)214 °CPhysProp
logP1.90SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.264 mg/mLALOGPS
logP2.13ALOGPS
logP1.1Chemaxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.31Chemaxon
pKa (Strongest Basic)-3.1Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area109.57 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity90.52 m3·mol-1Chemaxon
Polarizability37.56 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier-0.5727
Caco-2 permeable-0.6601
P-glycoprotein substrateSubstrate0.6985
P-glycoprotein inhibitor INon-inhibitor0.7714
P-glycoprotein inhibitor IINon-inhibitor0.8974
Renal organic cation transporterNon-inhibitor0.776
CYP450 2C9 substrateNon-substrate0.6019
CYP450 2D6 substrateNon-substrate0.8108
CYP450 3A4 substrateNon-substrate0.5091
CYP450 1A2 substrateNon-inhibitor0.7786
CYP450 2C9 inhibitorNon-inhibitor0.5713
CYP450 2D6 inhibitorNon-inhibitor0.8479
CYP450 2C19 inhibitorNon-inhibitor0.7738
CYP450 3A4 inhibitorInhibitor0.6198
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6625
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8224
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3534 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8884
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-016v-6598300000-da70dfe63bf7c73c6097
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0000900000-1f40bed1856f91ab8dd6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0000900000-1b28691ebe78d549eb4b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kr-1005900000-f6f0171070ec8783d766
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0079-1100900000-af58e7b7db92191d5bef
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0059-9031000000-1ad13c618ac499e30f6b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-1249300000-2777775b40a5c59c58cb
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-186.8673992
predicted
DarkChem Lite v0.1.0
[M-H]-195.50897
predicted
DeepCCS 1.0 (2019)
[M+H]+187.6533992
predicted
DarkChem Lite v0.1.0
[M+H]+198.70338
predicted
DeepCCS 1.0 (2019)
[M+Na]+187.2385992
predicted
DarkChem Lite v0.1.0
[M+Na]+207.44925
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity)
Specific Function
Atp binding
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [Article]
  3. Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG: Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol. 2002 Oct;283(4):F717-26. [Article]
  4. Gamba G: The thiazide-sensitive Na+-Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009 Oct;297(4):F838-48. doi: 10.1152/ajprenal.00159.2009. Epub 2009 May 27. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
Antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. Duarte JD, Cooper-DeHoff RM: Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802. doi: 10.1586/erc.10.27. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
Alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
Organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. Vallon V, Rieg T, Ahn SY, Wu W, Eraly SA, Nigam SK: Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. Am J Physiol Renal Physiol. 2008 Apr;294(4):F867-73. doi: 10.1152/ajprenal.00528.2007. Epub 2008 Jan 23. [Article]

Drug created at June 30, 2007 17:21 / Updated at February 21, 2021 18:51